List the three classes of bronchodilator drugs
- Beta-adrenoceptor agonists
- Anticholinergic drugs
- Phosphodiesterase inhibitors
List Beta adrenoceptor agonists
Beta 1 & Beta 2 non-selective:
Beta 2 selective:
- salbutamol, terbutaline
long acting Beta 2 agonists
- salmeterol, formoterol
List anticholinergenic drugs (prevent release of ACh)
- ipratropium; tiotropium (long acting)
Which class of bronchodilators do we use primarily for COPS?
As it is less reversible, we use all 3 categories
- B adrenoceptor agonists
Two telltale signs of asthma and what are they treated with?
- bronchocontriction with bronchodilators
- inflammation with corticosteroids
How would a cross section of a lumen look histologically when it has asthma?
- a little bit of mucus
- epithelium on airway
- basement membrane (blue) is thickened
- smooth muscle: much more than usual
- mucus sitting in the lumen
- oedema in the submucosa
Aim of Beta-2 adrenoceptor agonists?
To relax Airway Smooth Muscle (ASM) by binding to Beta-2 receptors on surface of ASM cells
Beta 2 adrenoceptor agonists can also have these effects besides relaxing airway smooth muscle (minor)
- inhibit mast cell release (LT, histamine)
- increase mucociliary clearance (by increasing ciliary beat frequency)
Outline the sensitisation (1st degree exposure) process in asthma
APC to T helper (IL-4) --> b cell --> IgE --> binds to Mast cells.
Salbutamol vs salmeterol on how it enters/affects the cell
- salbutamol directly goes and affects beta adrenoceptor
- we think salmeterol hangs around lipid membrane and 'leeches' out to the beta receptor adjacent
How does anticholinergics work at the Smooth Muscle receptors?
- Ach is released from the vagus efferent nerve.
- Anticholinergics dinds to the Ach receptors on the smooth muscle.
Pathway of Ach pathway to cause constriction (diagram)
(i) = inactive , (a) = active form
- Note B2 receptors that activates cAMP pathway
- Phosphorylated Myosin and Actin causes contraction.
Tiotropium vs ipratropium
- 10x more potent
- long acting version of anticholinergenic
- half life of 34.7h, while ipratropium has 0.25h.
- tiotropium has a prolonged blockade of M3 receptors
Downsides of PDE inhibitors?
- narrow therapeutic range (small difference between effective dose and dose causing side effects)
- side effects are nausea and vomiting
How do PDE inhibitors work intracellularly to relax muscle?
- cAMP is broken down by PDE to AMP.
- If we inhibit breakdown, we hav emore cAMP and hence more relaxation of muscle
List the isozymes of PDE in different tissues (airway, vascular, endothelium, neutrophil, T cell) (phosphodiesterase)
PDE I - V
- theophylline is non selective
Distribution in smooth muscle
Airway: II, IV, V
Vascular: III, IV
Endothelium III, IV
Neutrophil : IV
T Cell: IV
IV is the most common.
Asthma treatment: When should we take LABA's
We take it with ICS usually
- LABA + ICS for moderate to severe asthma
If bronchodilators don't work so well on people with COPD, how do we treat them?
- we still give them bronchodilators
> Beta adrenoceptor agonists
> theophylline (if they are already taking it)
- Long acting agents
> Tiotropium (once/day)
> Salmeterol, Formoterol
- ICS for advanced disease
> No decline in lung function
> decrease in exacerbation rate